Targeting the Major Groove of the Palindromic d(GGCGCC)2 Sequence by Oligopeptide Derivatives of Anthraquinone Intercalators

GC-rich sequences are recurring motifs in oncogenes and retroviruses, and could be targeted by non-covalent major-groove therapeutic ligands. We considered the palindromic sequence d(G1G2C3G4C5C6)2, and designed several oligopeptide derivatives of the anti-cancer intercalator mitoxantrone. The stability of their complexes with a 18-mer oligonucleotide encompassing this sequence in its center was validated using polarizable molecular dynamics. We report the most salient structural features of two novel compounds, having a dialkylammonium group as a side-chain on both arms. The anthraquinone ring is intercalated in the central d(CpG)2 sequence with its long axis perpendicular to that of the two base-pairs. On each strand, this enables each ammonium group to bind in-register to O6/N7 of the two facing G bases upstream. We subsequently designed tris-intercalating derivatives, each dialkylammonium substituted with a connector to an N9-aminoacridine intercalator extending our target range from six- to a ten-base pair palindromic sequence, d(C1G2G3G4C5G6C7C8C9G10)2. The structural features of the complex of the most promising derivative are reported. The present design strategy paves the way for designing intercalator-oligopeptide derivatives with an even higher selectivity, targeting an increased number of DNA bases, going beyond ten

Commande adaptative d'un positionneur en présence d'un frottement sec

Position control of a mechanical system is always executing faced with a static friction force more and less important.This friction force introduces a nonlinear and nonlinearisable part in the process.This force is very dependent on many parameters like velocit, temperature, and surface's states of mechanical parts.Thereby, this force is often viewed as a perturbation and different linear control methods such a GPS and LQG/LTR are brought into operation. To improve the performances of these controls, identification in real-time of static friction's characteristics and compensation of this disturbing force, with the control, are proposed.Identification of friction allows also to follow the wear of the system and to assure its maintenance.La commande en position d'un système mécanique s'effectue toujours en présence d'une force de frottement sec plus ou moins importante. Cette force de frottement introduit un terme non linéaire et non linéarisable dans le système à régler. Elle est de plus dépendante de nombreux paramètres comme la vitesse, la température et les états de surface des pièces mécaniques. De ce fait, elle est souvent considérée comme une perturbation et différentes méthodes de commande linéaire dont les commandes GPS et LQG/LTR sont mises en oeuvre. Pour améliorer les performances de ces commandes, on se propose d'identifier en temps réel la caractéristique du frottement sec et de compenser, avec la commande, cette force perturbatrice. L'identification du frottement permet également de suivre l'usure du système et d'assurer sa maintenance..

Commande adaptative d'un positionneur en presence d'un frottement sec

SIGLEINIST T 74951 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Commande adaptative d'un positionneur en presence d'un frottement sec

SIGLEINIST T 74951 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

The epimerization of peptide aldhydes - a synthetic study

International audienc

The 1,2,4-triazole as a scaffold for the design of ghrelin receptor ligands: development of JMV 2959, a potent antagonist

International audienc

Novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors

The present invention provides novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors according to formula (I) that are useful in the treatment or prophylaxis of physiological and/or pathophysiological conditions in mammals, preferably humans, that are mediated by GHS receptors. The present invention further provides GHS receptor antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular growth retardation, cachexia, short-, medium- and/or long term regulation of energy balance; short-, medium- and/or long term regulation (stimulation and/or inhibition) of food intake; adipogenesis, adiposity and/or obesity; body weight gain and/or reduction; diabetes, diabetes type I, diabetes type II, tumor cell proliferation; inflammation, inflammatory effects, gastric postoperative ileus, postoperative ileus and/or gastrectomy (ghrelin replacement therapy)

Novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors

The present invention provides novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors according to formula (I) that are useful in the treatment or prophylaxis of physiological and/or pathophysiological conditions in mammals, preferably humans, that are mediated by GHS receptors. The present invention further provides GHS receptor antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular growth retardation, cachexia, short-, medium- and/or long term regulation of energy balance; short-, medium- and/or long term regulation (stimulation and/or inhibition) of food intake; adipogenesis, adiposity and/or obesity; body weight gain and/or reduction; diabetes, diabetes type I, diabetes type II, tumor cell proliferation; inflammation, inflammatory effects, gastric postoperative ileus, postoperative ileus and/or gastrectomy (ghrelin replacement therapy)